In response to Research Topic 18. Functional Senescence: In this application we propose to adapt and validate automated, user friendly methods derived from statistical and condensed matter physics to quantify the local spatial organization of neurons in the cortex. In particular, our aim is to quantify the local microcolumnar organization of neurons by calculating the microcolumnar width, intermicrocolumnar distance, neuronal density within the microcolumn and the strength of microcolumnar order. This quantitative information on local microcolumnar organization will allow us to test the following hypotheses: (1) microcolumnar properties differ significantly across diverse cortical regions, (2) microcolumnar organization is disrupted in normal aging despite non-significant neuronal loss, (3) age-induced changes in microcolumnar organization are correlated with age-related cognitive decline. In our study we will validate and apply our methods to Nissl-stained, 30 microns thick frozen sections from three regions of the cerebral cortex: (a) area 46 of the prefrontal cortex in the lower bank of sulcus principalis, (b) area TE of the inferior temporal region below the superior temporal sulcus, and (c) area TL of the parahippocampal gyrus. These cortical regions were selected because they are potentially associated with cognitive impairments observed in normal aging and because they clearly differ in the degree of microcolumnarity when visually inspected under the microscope. We will compare the microcolumnar properties of these three regions in ten young and ten aged rhesus monkeys which have been previously behaviorally tested to assess learning, recognition memory, and executive system function. We will then use a regression analysis to determine if age-induced changes in microcolumar properties are related to alterations on any of these cognitive domains.